Despite considerable scientific progress over the past 15 years, notable limitations persist in the theoretical and clinical significance of memory assessment in persons with HIV-1 infection. The overarching aim of this revised multidisciplinary project is to provide a conceptually-driven approach to delineating the impact of HIV-1 infection on prospective memory (ProM). ProM is a unique aspect of episodic memory sensitive to fronto-striatal damage that encompasses the complex processes of forming, monitoring, and executing future intentions vis-a-vis ongoing distractions. Consideration of ProM can enhance prediction of- and interventions related to - instrumental activities of daily living (lADLs). It is therefore surprising that ProM has not been evaluated in HIV-1, especially given the fronto-striatal neuropathogenesis of HIV-1-associated memory deficits and their impact on lADLs. Accordingly, this revised research application is guided by the following specific aims: 1) to clarify the nature, extent, and disease correlates of ProM impairment in HIV-1 infection; 2) to delineate the cognitive mechanisms of ProM impairment in HIV-1 using both clinical and experimental measures; and 3) to assess the efficacy of ProM in predicting lADLs (e.g., medication adherence) in HIV-1. We will recruit 200 HIV+ participants and 50 demographically comparable controls to evaluate the following primary hypotheses: 1) HIV-1 infection is associated with deficient executive control of encoding and retrieval within ProM; 2) ProM impairment is associated with advanced HIV-1 disease (e.g., viral load); and 3) ProM provides incremental validity relative to traditional cognitive tests in predicting lADLs, including medication adherence. This study promises to produce important conceptual and practical innovations regarding the nature and clinical assessment of HIV-associated cognitive disorders, and may ultimately facilitate the development of ProM-based interventions to minimize the impact of cognitive disorders on persons with HIV-1 infection, caregivers, and the health care system.